Micropatterned surfaces have been used for regulating growth, migration and differentiation of various cell types on a variety of materials, and using a variety of topographical dimensions (see e.g. Folch et al, 2000; Thapa et al, 2003; Palmaz et al., 1999; and Miller et al, 2003). Typically, these studies are designed to promote growth of adherent cells in defined geometry—to micropattern adherent cells—, and to control their morphology, migration or differentiation. For example, when the substrate poly(lactic-co-glycolic acid) (PLGA) is micropatterned with 10, 20, and 30 μm wide channels separated by cell adhesion resistant copolymers of poly(OEGMA-co-MA) or poly-OEGMA, cultured fibroblasts reportedly spread exclusively within the channels and adopt elongated shapes along the channels (Lin et al, 2005).
Similarly, vascular smooth muscle cells (VSMCs) cultured on a micropatterned surface of 20 μm wide ridges of Nafion separated by 80 μm wide troughs of a cell resistant copolymer reportedly achieve parallel, single-file, end-to-end growth (Salloum et al, 2005). Spatial control over endothelial cell spreading and orientation was reportedly achieved by culturing the cells on micropatterned chitosan films with grooves separated by plateau regions coated with a material that resists cell adhesion (Wang and Ho, 2004), and a microscopic pattern of parallel grooves on a metallic surface increases endothelial cell migration rates (Palmaz et al, 1999).
We have previously reported that micropatterned matrix proteins and topography control VSCM morphology and function, wherein cells cultured on a PLGA surface micropatterned with channels 30 μm wide and 25 μm deep achieved an elongated morphology and reduced proliferation (Thakar et al, 2003).
During restenosis VSMCs convert from a contractile phenotype to a proliferative phenotype and migrate to the lumen of the artery, resulting in intimal hyperplasia, which is a significant cause of morbidity in patients with engineered vascular grafts. Various materials, coatings, drug impregnations, and designs have been employed in vascular grafts and stents to combat this invasion of VSMCs into the lumen of the artery.
Here we report that we can dramatically reduce VSMC proliferation on vascular devices by fabricating on the device surface very narrow and shallow elongate microgrooves. The mechanism behind this inhibitory phenomenon is not yet understood, but the subject groove cross-sectional dimensions apparently do not permit complete entrenchment of the VSMC as with prior art micropatterning.
Other Relevant References
Aspects of this invention were disclosed at the Nov. 7-10, 2004 American Heart Association (AHA) conference (New Orleans, La.), and the Oct. 13-16, 2004 Biomedical Engineering Society (BMES) conference (Philadelphia, Pa.)